Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJKHCY6)

• DOT Name: Nuclear pore complex protein Nup205 (NUP205)
• Synonyms: 205 kDa nucleoporin; Nucleoporin Nup205
• Gene Name: NUP205
• Related Disease:
  Acute myelogenous leukaemia
  Lung cancer
  Lung carcinoma
  Nephrotic syndrome, type 13
  Nephrotic syndrome, type 2
  Retinoblastoma
  Steroid-resistant nephrotic syndrome
  Venous thromboembolism
  Paget's disease
  Familial idiopathic steroid-resistant nephrotic syndrome
  Amyotrophic lateral sclerosis
  Bone Paget disease
• UniProt ID: NU205_HUMAN
• PDB ID: 5IJN; 5IJO; 7PER; 7R5J; 7R5K
• Pfam ID: PF11894
• Sequence:
  MATPLAVNSAASLWGPYKDIWHKVGNALWRRQPEAVHLLDKILKKHKPDFISLFKNPPKN
  VQQHEKVQKASTEGVAIQGQQGTRLLPEQLIKEAFILSDLFDIGELAAVELLLAGEHQQP
  HFPGLTRGLVAVLLYWDGKRCIANSLKALIQSRRGKTWTLELSPELASMTTRFTDELMEQ
  GLTYKVLTLVSQIDVNNEFEKLQRERGLGSEKHRKEVSDLIKECRQSLAESLFAWACQSP
  LGKEDTLLLIGHLERVTVEANGSLDAVNLALLMALLYCFDISFIEQSTEERDDMIHQLPL
  LTEKQYIATIHSRLQDSQLWKLPGLQATVRLAWALALRGISQLPDVTALAEFTEADEAMA
  ELAIADNVFLFLMESVVVSEYFYQEEFYIRRVHNLITDFLALMPMKVKQLRNRADEDARM
  IHMSMQMGNEPPISLRRDLEHLMLLIGELYKKNPFHLELALEYWCPTEPLQTPTIMGSYL
  GVAHQRPPQRQVVLSKFVRQMGDLLPPTIYIPYLKMLQGLANGPQCAHYCFSLLKVNGSS
  HVENIQGAGGSPVSWEHFFHSLMLYHEHLRKDLPSADSVQYRHLPSRGITQKEQDGLIAF
  LQLTSTIITWSENARLALCEHPQWTPVVVILGLLQCSIPPVLKAELLKTLAAFGKSPEIA
  ASLWQSLEYTQILQTVRIPSQRQAIGIEVELNEIESRCEEYPLTRAFCQLISTLVESSFP
  SNLGAGLRPPGFDPYLQFLRDSVFLRFRTRAYRRAAEKWEVAEVVLEVFYKLLRDYEPQL
  EDFVDQFVELQGEEIIAYKPPGFSLMYHLLNESPMLELALSLLEEGVKQLDTYAPFPGKK
  HLEKAVQHCLALLNLTLQKENLFMDLLRESQLALIVCPLEQLLQGINPRTKKADNVVNIA
  RYLYHGNTNPELAFESAKILCCISCNSNIQIKLVGDFTHDQSISQKLMAGFVECLDCEDA
  EEFVRLEEGSELEKKLVAIRHETRIHILNLLITSLECNPPNLALYLLGFELKKPVSTTNL
  QDPGVLGCPRTCLHAILNILEKGTEGRTGPVAVRESPQLAELCYQVIYQLCACSDTSGPT
  MRYLRTSQDFLFSQLQYLPFSNKEYEISMLNQMSWLMKTASIELRVTSLNRQRSHTQRLL
  HLLLDDMPVKPYSDGEGGIEDENRSVSGFLHFDTATKVRRKILNILDSIDFSQEIPEPLQ
  LDFFDRAQIEQVIANCEHKNLRGQTVCNVKLLHRVLVAEVNALQGMAAIGQRPLLMEEIS
  TVLQYVVGRNKLLQCLHAKRHALESWRQLVEIILTACPQDLIQAEDRQLIIRDILQDVHD
  KILDDEAAQELMPVVAGAVFTLTAHLSQAVLTEQKETSVLGPAEAHYAFMLDSCFTSPPP
  EENPLVGFASIGDSSLYIILKKLLDFILKTGGGFQRVRTHLYGSLLYYLQIAQRPDEPDT
  LEAAKKTMWERLTAPEDVFSKLQRENIAIIESYGAALMEVVCRDACDGHEIGRMLALALL
  DRIVSVDKQQQWLLYLSNSGYLKVLVDSLVEDDRTLQSLLTPQPPLLKALYTYESKMAFL
  TRVAKIQQGALELLRSGVIVRLAQCQVYDMRPETDPQSMFGMRDPPMFIPTPVDRYRQIL
  LPALQLCQVILTSSMAQHLQAAGQVLQFLISHSDTIQAILRCQDVSAGSLQELALLTGII
  SKAALPGILSELDVDVNEGSLMELQGHIGRFQRQCLGLLSRFGGSDRLRQFKFQDDNVEG
  DKVSKKDEIELAMQQICANVMEYCQSLMLQSSPTFQHAVCLFTPSLSETVNRDGPRQDTQ
  APVVPYWRLPGLGIIIYLLKQSANDFFSYYDSHRQSVSKLQNVEQLPPDEIKELCQSVMP
  AGVDKISTAQKYVLARRRLVKVINNRAKLLSLCSFIIETCLFILWRHLEYYLLHCMPTDS
  QDSLFASRTLFKSRRLQDSFASETNLDFRSGLAIVSQHDLDQLQADAINAFGESLQKKLL
  DIEGLYSKVRSRYSFIQALVRRIRGLLRISRN
• Function: Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. May anchor NUP62 and other nucleoporins, but not NUP153 and TPR, to the NPC. In association with TMEM209, may be involved in nuclear transport of various nuclear proteins in addition to MYC.
• Tissue Specificity: Expressed in the testis.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  Amyotrophic lateral sclerosis (hsa05014)
• Reactome Pathway:
  Transport of the SLBP independent Mature mRNA (R-HSA-159227)
  Transport of the SLBP Dependant Mature mRNA (R-HSA-159230)
  Transport of Mature mRNA Derived from an Intronless Transcript (R-HSA-159231)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)
  Rev-mediated nuclear export of HIV RNA (R-HSA-165054)
  Transport of Ribonucleoproteins into the Host Nucleus (R-HSA-168271)
  NS1 Mediated Effects on Host Pathways (R-HSA-168276)
  Viral Messenger RNA Synthesis (R-HSA-168325)
  NEP/NS2 Interacts with the Cellular Export Machinery (R-HSA-168333)
  Regulation of Glucokinase by Glucokinase Regulatory Protein (R-HSA-170822)
  Nuclear import of Rev protein (R-HSA-180746)
  Vpr-mediated nuclear import of PICs (R-HSA-180910)
  snRNP Assembly (R-HSA-191859)
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)
  SUMOylation of ubiquitinylation proteins (R-HSA-3232142)
  Nuclear Pore Complex (NPC) Disassembly (R-HSA-3301854)
  Regulation of HSF1-mediated heat shock response (R-HSA-3371453)
  SUMOylation of SUMOylation proteins (R-HSA-4085377)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  SUMOylation of RNA binding proteins (R-HSA-4570464)
  SUMOylation of DNA replication proteins (R-HSA-4615885)
  Transcriptional regulation by small RNAs (R-HSA-5578749)
  Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) (R-HSA-5619107)
  tRNA processing in the nucleus (R-HSA-6784531)
  HCMV Early Events (R-HSA-9609690)
  HCMV Late Events (R-HSA-9610379)
  Postmitotic nuclear pore complex (NPC) reformation (R-HSA-9615933)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  ISG15 antiviral mechanism (R-HSA-1169408)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Nephrotic syndrome, type 13	DIS7W7TI	Strong	Autosomal recessive	[3]
Nephrotic syndrome, type 2	DISIRFO1	Strong	Biomarker	[3]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[4]
Steroid-resistant nephrotic syndrome	DISVEBC9	Strong	Genetic Variation	[5]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[6]
Paget's disease	DISO3MC0	moderate	Genetic Variation	[7]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[8]
Bone Paget disease	DISIPS4V	Limited	Biomarker	[7]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear pore complex protein Nup205 (NUP205).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Nuclear pore complex protein Nup205 (NUP205).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[18]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear pore complex protein Nup205 (NUP205).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nuclear pore complex protein Nup205 (NUP205).	[22]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Nuclear pore complex protein Nup205 (NUP205).	[15]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Nuclear pore complex protein Nup205 (NUP205).	[19]

References

• [1] LncRNA SNHG1 overexpression regulates the proliferation of acute myeloid leukemia cells through miR-488-5p/NUP205 axis.Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5896-5903. doi: 10.26355/eurrev_201907_18334.
• [2] Critical function for nuclear envelope protein TMEM209 in human pulmonary carcinogenesis.Cancer Res. 2012 Aug 15;72(16):4110-8. doi: 10.1158/0008-5472.CAN-12-0159. Epub 2012 Jun 19.
• [3] Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nat Genet. 2016 Apr;48(4):457-65. doi: 10.1038/ng.3512. Epub 2016 Feb 15.
• [4] A Meta-Analysis of Retinoblastoma Copy Numbers Refines the List of Possible Driver Genes Involved in Tumor Progression.PLoS One. 2016 Apr 26;11(4):e0153323. doi: 10.1371/journal.pone.0153323. eCollection 2016.
• [5] Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome. J Clin Invest. 2018 Oct 1;128(10):4313-4328. doi: 10.1172/JCI98688. Epub 2018 Sep 4.
• [6] Identification of unique venous thromboembolism-susceptibility variants in African-Americans.Thromb Haemost. 2017 Apr 3;117(4):758-768. doi: 10.1160/TH16-08-0652. Epub 2017 Feb 16.
• [7] Genome-wide association identifies three new susceptibility loci for Paget's disease of bone.Nat Genet. 2011 May 29;43(7):685-9. doi: 10.1038/ng.845.
• [8] Dynamic mislocalizations of nuclear pore complex proteins after focal cerebral ischemia in rat.J Neurosci Res. 2017 Sep;95(9):1745-1759. doi: 10.1002/jnr.24005. Epub 2016 Dec 28.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [12] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [16] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [17] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [19] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [20] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [21] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.